AB0514 EXPRESSION OF IMMUNITY-RELATED GTPase FAMILY M PROTEIN (IRGM) SNPs AMONG EGYPTIAN LUPUS PATIENTS
Authors: M. Behiry, B. M Medhat, S. S. Ashour, D. Dorgham, A. Badr, A. Yamany
Journal: Annals of the Rheumatic Diseases (2022)

Background Of determinants that drives systemic lupus erythematosus (SLE) triggering and development is autophagy, Immunity-related GTPase family M protein (IRGM) was shown to be linked with immune -mediated diseases. Objectives Aim of the current study is to assess whether IRGM-autophagy gene polymorphism has a role in SLE susceptibility among Egyptian population and its relation to diverse clinical manifestations particularly lupus nephritis. Methods A cohort where total of 200 subjects (100SLE patients who fulfilling according to 2012 SLICC criteria and 100 controls) were enrolled. All patients underwent a thorough medical history and clinical examination. Lupus activity was evaluated by SLEDAI-2K score. Two single-nucleotide polymorphisms (SNPs) (rs10065172 &amp; rs4958846) were genotyped. Genotypes and Alleles analysis were conducted to compare between cases and controls as well as on the stratification analysis of presence or absence of lupus nephritis Results Among selected SNPs of IRGM, no association was considered between both SNPs and SLE susceptibility. For rs10065172, the major expressed genotype was CC (61% and 71%) (Adj OR= 2.9, 95%= 0.545-15.5) followed by TC (34 % and 27%) (Adj OR= 1.985, 95%= 0.357-11.041) in cases and controls respectively. For rs 4958847 AA and AG were comparably expressed in case (43% &amp;39%) and control (41%&amp;43%) with (Adj OR= 1.073, 95%= 0.483-2.382) and (Adj OR= 1.24, 95%= 0.557- 2.763) respectively. Additionally, no relation between both SNPs with gender, lupus nephritis, disease activity, or disease duration. Table 1. SNPs of rs 10065172, rs 4958847 genotypes and allele frequencies for cases and controls. IRGM a 10065172 Case N (%) Control N (%) p value unadjusted OR p value Adjusted OR 95th CI TT 5(5) 2(2) 0.445 0.388 0.252 TC 34(34) 27(27) 0.261 0.707 0.433 1.985 0.357-11.041 CC 61(61) 71(71) 0.161 1.525 0.211 2.9 0.545-15.5 IRGM4958847 GG 18(18) 16(16) 0.849 0.93 0.835 AG 39(39) 43(43) 0.565 1.1 0.598 1.24 0.557-2.763 AA 43(43) 41(41) 0.744 0.921 0.863 1.073 0.483-2.382 a IRGM: Immunity-related GTPase family M protein Conclusion IRGM SNPs (rs10065172 and rs4958846) is not associated with SLE susceptibility in this Egyptian cohort that necessitates further research to evaluate more the impact of IRGM autophagy-related gene on lupus. References [1]Yao QM, Zhu YF, Wang W, et al. Polymorphisms in Autophagy-Related Gene IRGM Are Associated with Susceptibility to Autoimmune Thyroid Diseases. Polymorphisms in Autophagy-Related Gene (IRGM) Are Associated with Susceptibility to Autoimmune Thyroid Diseases. Biomed Research International. 2018;2018:7959707. [2]Lee Y-K, Lee J-A. Role of the mammalian ATG8/LC3 family in autophagy: differential and compensatory roles in the spatiotemporal regulation of autophagy. BMB Rep. 2016;49:424 [3]Rai P, Janardhan KS, Meacham J, et al. IRGM1 links mitochondrial quality control to autoimmunity. Nat. Immunol . 2021;22:312-21. Disclosure of Interests None declared